4 iron-4sulfur Clusters in Aging and Alzheimer's Disease

4 铁-4 硫簇在衰老和阿尔茨海默病中的作用

• 批准号: 6532458
• 负责人: VALTER D. LONGO
• 金额: $ 9.83万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532458
• 关键词: Alzheimer's disease; NAD(P)H dehydrogenase; PC12 cells; aconitate hydratase; aerobiosis; aging; amyloid proteins; creatine kinase; electron spin resonance spectroscopy; enzyme activity; enzyme linked immunosorbent assay; fluorescence spectrometry; genetically modified animals; histochemistry /cytochemistry; immunoprecipitation; iron sulfur protein; laboratory mouse; magnetic resonance imaging; neurons; oxidative stress; statistics /biometry; succinate dehydrogenase; superoxides; tissue /cell culture; western blottings

DESCRIPTON (Provided by applicant): The candidate was trained as a biochemist at UCLA where he specialized in studies of oxidative damage in yeast. Dr. Longo has spent the past three years as a PI of a funded yeast laboratory and as a Research Associate/Assistant Professor working on Alzheimer?s Disease-related projects. The candidate?s long-term career goals are to be a faculty member in a neuroscience program and to continue research on aging. He is applying for the K01 Award in Aging to develop his research skills and knowledge in the neuroscience field with particular focus on the fundamental mechanisms of oxidative damage in aging and neurodegenerative diseases. Dr. Caleb. Finch, Prof. of Gerontology, Neuroscience, and Molecular Biology at the Andrus Gerontology Center, will act as Dr. Longo?s mentor along with Prof. Kelvin Davies. The international stature of these faculty members in the field of aging, oxidative stress, and neurodegenerative diseases, make this environment ideal for the development of Dr. Longo expertise in these fields. Dr Longo will participate in the bimonthly chalk talks in the Neurobiology and Endocrinology of Aging, will attend the weekly research seminars and journal clubs in USC?s multidisciplinary neuroscience program, and will attend a course on the responsible conduct of research. The candidate will also be exposed to clinical studies on cognitive changes during normal aging and during Alzheimer disease (AD). The research project "4 Iron-4 Sulfur Clusters in Aging and Alzheimer?s Disease" proposes to test the hypothesis that the 4Fe-4S clusters, contained in certain dehydratase enzymes sensitive to superoxide toxicity, are a major source of the redox-active iron that mediates oxidative damage during aging and in Alzheimer?s Disease. This hypothesis will be tested by measuring redox-active iron in animal models for AD and by determining the contribution of 4Fe-4S clusters to the pool of redox-active iron and to oxidative damage and death in neurons and neuronal cell lines exposed to oxidants and beta amyloid.

描述（由申请人提供）：该候选人接受过生物化学家培训 在加州大学洛杉矶分校，他专门研究酵母的氧化损伤。博士。 过去三年来，Longo 一直担任一家受资助的酵母实验室的 PI， 作为研究助理/助理教授，研究阿尔茨海默氏病相关问题 项目。候选人的长期职业目标是成为一名教师 神经科学项目的成员，并继续研究衰老问题。他是 申请老龄化领域的 K01 奖以发展他的研究技能和 神经科学领域的知识，特别关注基础知识 衰老和神经退行性疾病中氧化损伤的机制。博士。 迦勒。芬奇，老年学、神经科学和分子生物学教授 安德鲁斯老年学中心将与隆戈教授一起担任隆戈博士的导师。 凯尔文·戴维斯。这些教师在该领域的国际地位 衰老、氧化应激和神经退行性疾病，使这 环境非常适合隆戈博士发展这些领域的专业知识。 Longo 博士将参加神经生物学和 衰老内分泌学，将参加每周的研究研讨会和期刊 南加州大学多学科神经科学项目的俱乐部，并将参加 关于负责任的研究行为的课程。该候选人还将 接受有关正常衰老过程中认知变化的临床研究， 阿尔茨海默病（AD）期间。研究项目“4铁-4硫团簇 在衰老和阿尔茨海默氏病中”提出检验以下假设： 4Fe-4S簇，包含在某些对水敏感的脱水酶中 超氧化物毒性是介导氧化还原活性铁的主要来源 衰老过程中和阿尔茨海默病中的氧化损伤。这个假设将 通过测量 AD 动物模型中的氧化还原活性铁进行测试，并通过 确定 4Fe-4S 簇对氧化还原活性池的贡献 铁对神经元和神经元细胞系的氧化损伤和死亡 暴露于氧化剂和β淀粉样蛋白。